The objectives of this proposal are to continue our studies of: 1) muscle abnormalities in patients with acute schizophrenia or affective psychoses, and their first-degree relatives and 2) 3 types of rat experiments, involving restraint stress, Phencyclidine (Sernyl R, Phen, a potent psychotomimetic drugs), and epinephrine which produce increased plasma creatine phosphokinase (CPK) levels and skeletal muscle abnormalities and thus may be useful as model systems for the study of the muscle abnormalities in acutely psychotic patients. The human studies will involve the determination throughout hospitalization of the level of CPK in serum and its correlation with psychopathology, prognostic variables, daily clinical state, outcome of treatment, and muscle biopsy findings. Additional evidence for muscle abnormalities will be sought with exercise tests and EMG's. Studies on non-specific factors which might cause muscle abnormalities will be continued. Investigation of specific hypotheses of the etiology of muscle abnormalities will be undertaken in psychotic patients: e.g. presence of muscle toxins in sera; effect of sleep deprivation; and membrane abnormalities of muscle and blood platelets. The rat studies will involve the use of pharmacologic agents to define how Phen and restraint at room temperature (RRT) or epinephrine increase PCPK levels and produce muscle abnormalities. Approaches to be used include the use of drugs which share some pharmacologic or biochemical properties with Phen, block the effects of Phen, or influence bioamine metabolism. The role of some endocrine secretions in the Phen-RRT muscle effects will be studied. The usefulness of brain lesions or brain stimulation to define which brain regions are crucial to the behavioral effects of Phen and Phen-RRT will be studied. In vitro incubations of rat skeletal muscle will also be used to investigate the mechanism of Phen action. The mechanism by which restraint at 2 degrees C produces muscle abnormalities will also be studied.